Abstract:

Anosognosia, a defect in self-awareness of cognitive deficit, is frequently observed in Alzheimer’s disease (AD),
and has been linked to temporal lobe pathology. Since amyloid deposition in AD begins many years prior to clinical
dementia, we hypothesized that early alterations in awareness of memory performance might be associated with
occult amyloid deposition in clinically normal older subjects.

Thirty-six cognitively normal (CDR 0) subjects underwent neuropsychological assessment and PiB PET imaging.
The Memory Function Questionnaire “Frequency of Forgetting” (FoF) variable was used as a measure of selfawareness
of memory functioning, and actual memory performance was measured with the 12-word Selective
Reminding Test “Delayed Recall” (DR) variable. We calculated an Anosognosia Ratio (AR) for each subject as
[self-assessment – actual performance] divided by [self-assessment + actual performance] (range -1.0 to 1.0).
More positive scores indicate an overestimation of memory performance, similar to anosognosia, while more
negative scores indicate an underestimation of memory performance. A score of 0 is an accurate estimation of
performance.

Higher AR score was associated voxel-wise with greater PiB retention (DVR) in the inferior temporal lobe
(Z=4.33, voxel-level corrected p=0.03; cluster-level corrected p=0.02). AAL ROI analyses confirmed that
subjects who overestimated performance (n=20) had greater PiB retention in medial and lateral temporal
cortex, hippocampus, fusiform and amygdala compared to those who did not overestimate performance
(n=16; pWe conclude that clinically normal older adults who overestimated their own memory performance had greater
amyloid burden in multiple temporal regions. In addition, amyloid was related to mild memory impairment in the
full sample. Clinical follow-up will be required to determine whether these individuals develop memory impairment,
signs of anosognosia, or AD.